Specific active site inhibitors of enzymes or substrate binding partners and methods of producing same

Patent metadata

Field	Value
Publication number	US-10562945-B2
Application number	US-201916239784-A
Country	US
Kind code	B2
Filing date	Jan 4, 2019
Priority date	Aug 10, 2010
Publication date	Feb 18, 2020
Grant date	Feb 18, 2020

Abstract

The present disclosure provides a method of producing enzyme-specific inhibitors or substrate binding partners comprising: identifying active site residues of the substrate in the enzyme substrate complex or in substrate binding partner-substrate complex; randomizing the active site residues to produce a combinatorial library of substrate variants; and selecting substrate variants that inhibit enzyme activity or bind substrate as substrate-specific binding partners. The present disclosure also provides ubiquitin enzyme specific inhibitors and ubiquitin variants that bind ubiquitin interaction motifs.

First claim

The invention claimed is:

1. A specific inhibitor of a deubiquitinating enzyme, wherein the deubiquitinating enzyme is USP21, and wherein the inhibitor of USP21 is a ubiquitin variant comprising the amino acid sequence set forth in any of SEQ ID NO: 5, 6, or 7.

2. The inhibitor of claim 1 , wherein the ubiquitin variant comprises the amino acid sequence set forth in SEQ ID NO: 5.

3. The inhibitor of claim 1 , wherein the ubiquitin variant comprises the amino acid sequence set forth in SEQ ID NO: 6.

4. The inhibitor of claim 1 , wherein the ubiquitin variant comprises the amino acid sequence set forth in SEQ ID NO: 7.

Assignees

• Governing Council Univ Toronto

Inventors

• Sidhu Sachdev
• Beatty Linda
• Ernst Andreas

Classifications

• A61K38/17

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• C07K14/47 Primary

  from mammals · CPC title

• C07K14/435 Primary

  from animals; from humans · CPC title